Design, Synthesis and Biological Activities Evaluation of Novel Pterostilbene-Urea Derivatives as Potential Anti-Inflammatory Agents.

1. The toxicity of derivatives was removed by the reasonable modification of bioactive skeleton. 2. As potential COX-2 inhibitor with IC values ranging from 39.42 to 179.84 nM/L, compounds (Q4-Q10, Q20) exhibited superior anti-inflammatory activity at low micromolar concentrations. 3. Q7 (IC= 61.05 nM/L), Q10 (IC= 54.68 nM/L) and Q20 (IC= 39.42 nM/L) showed stronger COX-2 inhibitory abilities than Celecoxib (IC= 67.89 nM/L). 4. The strongest anti-inflammatory agent, Q20 (IC= 9.96 μM/L, IC= 39.42 nM/L) effectively inhibited the secretion of IL-1β and TNF-α, exhibited the IC values of 12.30 and 9.07 μM/L respectively. 5. Q20 exerted as anti-inflammatory actives via targeting COX-2, down-regulating iNOS and TLR4 protein, and inhibiting the activation of NLRP3 inflammasome and NF-κB signal pathway.